Triptolide alleviates pathological neovascularisation in oxygen-induced retinopathy via inhibiting the inflammation mediated by NF-κB pathway

Abstract

Background Retinopathy of prematurity (ROP), an oxygen-induced retinopathy (OIR), triggers a series of vascular lesions and inflammatory responses and results in visual impairment or even blindness. Triptolide (TP) possesses many pharmacological properties, including immunosuppressive and anti-tumour effects. However, the effects of TP on ROP and its underlying mechanisms remain unclear. Purpose To investigate whether TP could inhibit the progression of OIR and to elucidate its underlying mechanisms. Methods The 7-day-old mice (P7) were kept in a 75% hyperoxia incubator for 5 days to induce an OIR model, followed by TP treatment for 5 days. Biomedical analysis and histopathological examinations of harvested retinas were conducted to explore the effect of TP. Furthermore, the impact of TP on retinal neovascularisation and microglial activation was validated using human umbilical vein endothelial cells (HUVECs) and human microglial clone 3 cells (HMC3s). Results TP treatment could significantly alleviate retinal pathological neovascularisation by inhibiting microglial activation. It downregulated the elevated levels of inflammatory cytokines (inducible nitric oxide synthase, tumour necrosis factor-α, Cox2 and interleukin (IL)-1β) and angiogenesis-related factors (hypoxia-inducible factor-1α, matrix metalloproteinase-2 and vascular endothelial growth factor-A) in OIR retinas and hypoxic HMC3s. HUVECs’ migration, proliferation and tube-forming capacities were also markedly suppressed under TP treatment. Further analysis suggested that TP exerted its anti-angiogenic effect in a way similar to NF-κB inhibitor (BAY117082). Conclusion TP alleviates pathological neovascularisation in OIR, potentially through the inhibition of inflammation mediated by NF-κB pathway. Data are available upon reasonable request. On reasonable request, the corresponding authors will provide the data that underpins the study's conclusions.